胰岛素抵抗大鼠骨骼肌组织中糖原合成酶激酶-3的表达及意义

目的:观察饮食诱导的胰岛素抵抗(IR)大鼠骨骼肌组织中糖原合成酶激酶3(GSK3)的表达变化状况,探讨GSK3在IR发生过程中的作用。方法:将40只Wistar大鼠随机分为正常组、模型组、饮食组和运动组,每组10只。模型组、饮食组和运动组均喂以高糖高脂饲料,4周后饮食组大鼠改以常规饲料喂养6周,运动组则继续在高糖高脂饲料基础上加以游泳运动6周。定期检测大鼠体质量(BW)、血甘油三脂(TG)和胆固醇(TC)、空腹血糖(FPG)和胰岛素水平(FINS),计算胰岛素敏感指数(ISI),并于11周后采用Westernblot法检测各组大鼠骨骼肌中GSK3的含量。结果:高脂高糖饮食4周后,模型组、饮食组及运动组大鼠的FPG水平与正常组比较差异不明显(P>0.05),但FINS水平均明显高于正常组,ISI均明显低于正常组,差异均有统计学意义(P<0.05)。饮食组与运动组分别经过6周的干预后,饮食组与模型组相比,FPG、FINS水平均明显降低,ISI明显升高,差异有显著性(P<0.05),运动组与模型组相比,FPG、FINS水平也明显降低,ISI明显升高,差异有显著性(P<0.05)。Westernblot结果示模型组、饮食组及运动组大鼠骨骼肌中GSK3的含量均较正常组增高(P<0.05),且饮食组与运动组大鼠骨骼肌中GSK3的含量分别较模型组减少23.22%(P<0.01)及27.24%(P<0.01)。结论:饮食控制和运动锻炼均可显著降低空腹血糖和胰岛素水平,增加胰岛素敏感性,其机制与细胞中GSK3蛋白表达水平降低有关。

Relationship Between the Protein Level of Glycogen Synthase Kinase-3 and Insulin Resistance in Skeletal Muscle of Wistar Rats with High-fat and High-sucrose Diets

Objective: To observe the relationship between glycogen synthase kinase-3 and insulin resistant in skeletal muscle of Wistar rats induced by high-fat/high-sucrose diets. Methods: Forty Wistar rats were divided into four groups randomly as the control group, model group, diet group and exercise group. The model group, diet group and exercise group were given the high-fat and sucrose diets (20% sucrose, 10% lard, 2.5% cholesterol and 1% cholic acid) for four weeks. Then the diet group were fed with normal diets and exercise group were trained by swimming regularly for six weeks. Body weight(BW), serum triglyceride(TG)and cholesterol(TC), fasting plasma glucose(FPG) and serum insulin concentration(FINS) were measured and insulin sensitivity index(ISI) was calculated as well. At the end of the experiment for 11 weeks, GSK-3 protein was detected by Western blot analysis. Results: After four weeks of the high-fat/high-sucrose diets, FPG levels were unchanged in model group, diet group and exercise group(P>0.05), while FINS increased and ISI decreased in all these groups(all P<0.05) compared with the control group. As compared with model group, FPG and FINS in diet group decreased significantly(both P<0.05), yet ISI of these rats increased markedly(P<0.05)after given normal diet for six weeks. And the same alterations appeared in exercise group rats after six weeks of exercise. The outcome of Western blot showed that the expression of GSK-3 in skeletal muscle of model group increased by 70.20%(P<0.01)compared with the control group. After six weeks of diet control or exercise training, the GSK-3 protein in skeletal muscle of diet group and exercise group rats decreased by 23.22%(P<0.01)and 27.24%(P<0.01) respectively compared with the model group. Conclusion: GSK-3 in skeletal muscle of fat rats group was significantly higher than that in the control group. Diet control and exercise training can also lower the expression of GSK-3 in skeletal muscle of insulin resistance rats. GSK-3 played an important role in the insulin resistance of obesity.